The role of biological ions as mediators of cellular activity is well established. In U.S. patent application Ser. No. 923,760, now U.S. Pat. No. 4,818,697, the inventors of the present invention disclose novel techniques for controlling the movement of a preselected ionic species across the membrane of a living cell. Therein, the relationship between ion movement and fluctuating magnetic fields is described and a method and apparatus are provided by which ion movement can be selectively controlled. Having discovered that ion movement through a biochemical membrane can be controlled by creating a specific relationship between the strength of a fluctuating magnetic field and the rate of the field oscillation, and that the relationship can be predicted using the cyclotron resonance equation, the frequency of which is: ##EQU1## the present inventors provided a foundation on which a number of useful inventions are based.
Accordingly, in U.S. patent application Ser. No. 923,760, it is disclosed that by exposing a region of living tissue of a subject such as a human or animal subject to an oscillating magnetic field of predetermined flux density and frequency, the rate of tissue growth can be controlled. Specifically, it is disclosed therein that by tuning a fluctuating magnetic field to the specific cyclotron resonance frequency of a preselected ion such as Ca.sup.++ or Mg.sup.++, the rate of bone growth can be stimulated. It is anticipated that this treatment will be highly beneficial in the treatment of fractures, bone non-unions, and delayed unions. In addition, the use of cyclotron resonance tuning to control the growth rate of non-osseous, non-cartilaginous connective solid tissue is described in U.S. patent application Ser. No. 254,438, now U.S. Pat. No. 5,106,361. In U.S. patent application Ser. No. 265,265, now U.S. Pat. No. 5,067,940, a method and apparatus based on cyclotron resonance tuning are disclosed which allow the growth rate of cartilaginous tissue to be regulated. Still another important use of cyclotron resonance tuning, one of particular significance in the treatment of elderly patients, is disclosed in U.S. patent application Ser. No. 295,164. Therein, a method and apparatus for treating and preventing osteoporosis, both locally and systemically, is set forth. Therefore, it will be appreciated that cyclotron resonance regulation of ion movement is instrumental in a number of highly beneficial inventions in the field of medicine.
As described more fully in the foregoing United States patent applications, the inventors of the present invention discovered that ion movement through cell membranes can be achieved with the use of a magnetic field generating device in connection with an oscillator for creating a fluctuating magnetic flux density where a predetermined relationship between frequency and field strength is established. Preferably the magnetic field generating device includes a pair of Helmholtz coils. A cell or region of tissue, such as bone, cartilage or the like, is positioned between the Helmholtz coils such that a uniform magnetic field of controlled parameters permeates the target cell or tissue. As will be appreciated, in most instances the cell or tissue which is exposed to the applied magnetic field is also subject to a local magnetic field having a component in the direction of the applied field. In these applications, a magnetic field sensing device is provided to measure the combined or total magnetic flux, i.e. the sum of the applied magnetic field parallel to an axis which extends through the cell and the component of the local field in this direction.
In the preferred embodiments of the foregoing inventions, the charge-to-mass ratio of an ion, the transmembrane movement of which is to be regulated, is used to determine the frequency at which the applied magnetic field is oscillated to provide a predetermined relationship between the charge-to-mass ratio of the ion and the strength and frequency of the magnetic field. This relationship is determined using the cyclotron resonance equation, f.sub.c =Bq/2.pi.m, where f.sub.c is the frequency of the oscillating magnetic field in Hertz, q/m is the charge-to-mass ratio of the ion in Coulombs per kilograms, and B is a non-zero average value of the magnetic flux density in Tesla along the axis permeating the subject cell or tissue. When the field includes a component of the local filed, this value is a non-zero net average value of the combined or resultant magnetic field.
The present invention is directed toward certain modifications in cyclotron resonance regulation of ion movement. More specifically, the present invention addresses the desirable goal of simultaneously regulating transmembrane movement of two different ionic species, for example Ca.sup.++ and Mg.sup.++, and also to additional frequencies which are effective for a single ion.
Therefore, it is an object of the present invention to provide a method and apparatus by which the movement of a single ionic species across a cell membrane can be regulated by a fluctuating magnetic field having a frequency selected from a group of frequencies based on the fundamental cyclotron resonance frequency. It is a further object of the present invention to provide .epsilon. method and apparatus by which the transmembrane movement of two or more distinct ionic species in a single system may be simultaneously regulated using a fluctuating magnetic field having a predetermined ratio between the frequency and average field strength. It is still a further object of the present invention to provide a number of techniques for the therapeutic treatment of biological subjects which are based on the tuning principles set forth herein.